In the human body, blood clots form and dissolve by dynamic processes. Blood clots primarily comprise fibrin, which can be broken down by plasmin in a process known as fibrinolysis. Plasmin is derived from plasminogen, which is formed in the liver and flows freely in the circulatory system. The conversion of plasminogen to plasmin is catalyzed by plasminogen activators, such as urokinase. Urokinase is produced in the kidney and is found naturally in the blood and urine. It circulates in an inactive single-chain form and is converted into an active two-chain form in the presence of plasmin.
The initiation of fibrinolysis is useful for a variety of medical treatments, such as the treatment of patients suffering from acute vascular diseases. Since urokinase causes the initiation of fibrinolysis, it has significant medical utility. Urokinase is especially effective for the treatment of vascular diseases characterized by thrombosis or thromboembolism. In addition to its medical utility for breaking down existing blood clots, urokinase also is useful for inhibiting the formation of new blood clots.
Methods for the production of human urokinase that rely on the isolation of urokinase from blood or urine have been described (see, for example, U.S. Pat. No. 5,156,967). Other conventional methods rely on recombinant DNA techniques (see, for example, U.S. Pat. No. 5,112,755). Unfortunately, most conventional techniques for the production of urokinase are complex and expensive and are not designed to produce large quantities of urokinase. Thus, a need remains for methods for producing urokinase.